JP 11130750, published on 18 May 1999, describes amongst others, substituted phenylaminocarbonylindolyl derivatives as 5-HT receptor antagonists.
EP1129074, published on 18 May 2000, describes anthranilic acid amides as inhibitors of vascular endothelial growth factor receptors (VEGFR) and useful in the treatment of angiogenic disorders.
WO01/42224, published on 14 Jun. 2001, provides carboxyamido derivatives for the treatment of Alzheimer disease.
EP1317443, published on 21 Mar. 2002, discloses tricyclic tert-amine derivatives, useful as chemokine receptor CXCR4 or CCR5 modulators for treating human immunodeficiency virus and feline immunodeficiency virus.
EP1379239, published on 10 Oct. 2002, discloses N-(2-arylethyl)benzylamines as antagonists of the 5-HT6 receptor.
WO00/15357, published on 23 Mar. 2000, provides piperazine-4-phenyl derivatives as inhibitors of the interaction between MDM2 and p53. EP1137418, published on 8 Jun. 2000, provides tricyclic compounds for restoring conformational stability of a protein of the p53 family.
WO03/040402, published on 15 May 2003, provides compounds that inhibit the interactions between proteins, such as the interaction between MDM2 and p53.
EP1443937, published on 22 May 2003, describes substituted 1,4-benzodiazepines and the uses thereof as inhibitors of the MDM2-p53 interactions.
EP1458380, published on 26 Jun. 2003, provides cis-2,4,5-triphenyl-imidazolones that inhibit the interaction of MDM2 protein with p53-like peptides and have antiproliferative activity.
EP1519932, published on 15 Jan. 2004, discloses bisarylsulfonamide compounds that bind to MDM2 and can be used in cancer therapy.
EP1809622, published on 30 Mar. 2006, discloses inhibitors of the interaction between MDM2 and p53.
There is a need for effective small molecules that inhibit the interactions between MDM2 and p53, have potent inhibitory effect against tumor cell growth, have a broad safety profile and less undesired side effects.
The compounds of the present invention show excellent in-vitro activity. They have low affinity for the P450 enzymes which reduces the risk of adverse drug-drug interaction allowing for a wider safety margin. Moreover, the compounds of the present invention show excellent in vivo anti tumor effects while having less in vivo drug induced neurological effects.